Hepcidin, a peptide hormone typically existing in two forms made of either 20 or 25 amino acids, is expressed and secreted by a number of cells in response to iron loading and inflammation. Hepcidin is produced predominantly in hepatocytes of the liver, plays a central role in the regulation of iron homeostasis, acts as an antimicrobial peptide and is directly or indirectly involved in the development of most iron-deficiency/overload syndromes. A major action of hepcidin is to internalize and degrade the iron exporter ferroportin, which is expressed on all iron-exporting cells. Hepcidin directly binds to ferroportin. A high hepcidin level thus leads to the suppression of intestinal iron absorption and iron release from macrophages and hepatocytes, while a low concentration of hepcidin leads to acceleration of iron release from these cells.
Hepcidin is also suspected to play role in pathogenesis of anemia of inflammation and iron-deficiency anemia. Anemia of inflammation, also known as anemia of chronic disease (ACD) or anemia of chronic disorders, currently is the most frequent anemia among hospitalized patients and a common syndrome complicating many infectious, non-infectious inflammatory and neoplastic disorders. ACD is a normocytic, normochromic anemia characterized by decreased iron and iron-binding capacity (transferrin), increased ferritin and the presence of iron in bone marrow macrophages, indicating impaired mobilization of iron from its stores. While in anemia of inflammation hepcidin levels are increased, in iron-deficiency anemia low hepcidin levels are found. Hence, hepcidin could be used as a marker to distinguish these diseases. Hepcidin may also be a useful marker for screening, prognosis and monitoring hereditary hemochromatosis and iron loading anemias. Hepcidin levels may further be useful in monitoring EPO treatment and predicting a response to EPO.
Methods of isolating, analyzing and quantifying hepcidin as well as agents for the treatment of diseases and conditions associated with hepcidin have been described in international patent applications WO 2008/011158, WO 2008/097461, WO 2009/094551A1, WO 2009/139822, WO 2009/058797 and WO 2010/017070. However, no hepcidin-binding protein having the features attendant to the proteins provided by present invention has been previously described.